Inflammatory events based upon response to antigen have been implicated in a variety of middle ear disorders including otitis media with effusion (OME). Immune responses are also intimately involved in host response to infection at this site. Investigation of the role of immunity in middle ear disorders has been hampered by a lack of basic information concerning the nature and sequelae of immune responses as they operate in the unique environment of the middle ear cavity. To address this lack, animal models of immune response in the middle ear have been developed and used to investigate the properties of immunity at this site. Areas to be studied in the present application include local production of various immunoglobulin classes in the middle ear, the potential existence of specific homing by lymphocytes to the middle ear mucosa, and the role of the eustachian tube in antigen clearance. Models of both acute and chronic immune-mediated OME have also been developed and used to explore the immune and inflammatory events which have the potential to contribute to OME. Experiments proposed include determination of whether passive sensitization with IgG1, IgG2 or IgE will transfer immune-mediated OME, exploration of the role of the eustachian tube in immune-mediated OME, determination of whether local immune response can reduce inflammation which results from expression of systemic immunity in the middle ear, and investigation of the effects of prior viral infection on middle ear immune response. The importance of several inflammatory mediators in the generation of middle ear effusion and inflammation will be assessed by direct assay of experimental effusions, and by introduction of extracted and purified mediators into the middle ear cavity. Intervention in immune-mediated OME will be explored utilizing pharmacologic agents which inhibit suspected immune and inflammatory pathways. This will both test the feasibility of intervention and provide information concerning the importance of targeted inflammatory pathways in immune-mediated middle ear disease.